Oral Intake of Hydrogen-rich Water Inhibits Intimal Hyperplasia in Arterialized Vein Grafts in Rats

Abstract

AimsArterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. Methods and resultsThe inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H 2 O Mg (OH) 2 + H 2 ). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. ConclusionDrinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life.--

Potential ghrelin-mediated benefits and risks of hydrogen water

“…Regular ingestion of hydrogen water was found to inhibit atherogenesis in atheroma-prone apolipoprotein E knockout mice [95]. Similarly, hydrogen water consumption suppressed intimal hyperplasia in arterialized vein grafts in rats [96]. In patients with metabolic syndrome, 8-10 weeks of hydrogen water ingestion was associated with favorable effects on serum lipid profile (reduced LDL cholesterol and apoB, increased HDL cholesterol), like those seen in a pre-clinical study with Syrian hamsters [97][98][99] (long-term administration of the ghrelin mimic MK-677 likewise decreased LDL cholesterol [31]).…”

Hydrogen: Therapeutic Potential in Wellness and Medicine

“…Hydrogen-enriched water (0.5 or 0.6 mM) has also been shown to protect rat cardiac allografts from oxidative injury and inflammation-associated deterioration, with significant reductions in markers of oxidative injury and of inflammation (p<0.05), thereby increasing allograft survival (46). Moreover, hydrogenenriched water (0.55-0.65 mM) inhibited intimal hyperplasia and reduced oxidative damage in arterialized vein grafts in rats (47). Inhaled hydrogen (2%) appears to have beneficial effects in models of lung and intestinal transplantation, including improved spontaneous muscle contractile activity, reduced expression of inflammatory mediators and oxidative injury, prevention of IRI and improved graft survival (48,49).…”